A HOMOLOG OF DROSOPHILA-AURORA KINASE IS ONCOGENIC AND AMPLIFIED IN HUMAN COLORECTAL CANCERS

Genetic and biochemical studies in lower eukaryotes have identified se veral proteins that ensure accurate segregation of chromosomes. These include the Drosophila aurora and yeast Ipl1 kinases that are required for centrosome maturation and chromosome segregation. We have identif ied two human homologues of these genes, termed aurora1 and aurora2, t hat encode cell-cycle-regulated serine/threonine kinases. Here we demo nstrate that the aurora2 gene maps to chromosome 20q13, a region ampli fied in a variety of human cancers, including a significant number of colorectal malignancies. We propose that aurora2 may be a target of th is amplicon since its DNA is amplified and its RNA overexpressed, in m ore than 50% of primary colorectal cancers. Furthermore, overexpressio n of aurora2 transforms rodent fibroblasts. These observations implica te aurora2 as a potential oncogene in many colon, breast and other sol id tumors, and identify centrosome-associated proteins as novel target s for cancer therapy.